Premium
Hypoglycaemia leads to a delayed increase in platelet and coagulation activation markers in people with type 2 diabetes treated with metformin only: Results from a stepwise hypoglycaemic clamp study
Author(s) -
Aberer Felix,
Pferschy Peter N.,
Tripolt Norbert J.,
Sourij Caren,
Obermayer Anna M,
Prüller Florian,
Novak Eva,
Reitbauer Philipp,
Kojzar Harald,
Prietl Barbara,
Kofler Selina,
Brunner Martina,
Svehlikova Eva,
Stojakovic Tatjana,
Scharnagl Hubert,
Oulhaj Abderrahim,
Aziz Faisal,
Riedl Regina,
Sourij Harald
Publication year - 2020
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.13889
Subject(s) - platelet activation , metformin , medicine , platelet , type 2 diabetes , coagulation , von willebrand factor , endocrinology , hemostasis , glycated hemoglobin , diabetes mellitus , hypoglycemia
Aims To investigate the effect of hypoglycaemia on platelet and coagulation activation in people with type 2 diabetes. Materials and methods This monocentric, open, single‐arm, mechanistic trial included 14 people with established type 2 diabetes (four women, 10 men, age 55 ± 7 years, glycated haemoglobin concentration 51 ± 7 mmol/mol) receiving metformin monotherapy. A stepwise hyperinsulinaemic‐hypoglycaemic clamp experiment (3.5 and 2.5 mmol/L, for 30 minutes respectively) was performed, aiming to investigate platelet and coagulation activity during predefined plateaus of hypoglycaemia, as well as 1 day and 7 days later. Results While platelet activation assessed by light transmittance aggregometry did not significantly increase after the hypoglycaemic clamp procedure, the more sensitive flow cytometry‐based measurement of platelet surface activation markers showed hypoglycaemia‐induced activation 24 hours (PAC1 pos CD62P pos , PAC1 pos CD63P pos and PAC1 pos CD62P pos CD63 pos ; P < .01) and 7 days after the hypoglycaemic clamp ( P < .001 for PAC1 pos CD63 pos ; P < .01 for PAC1 pos CD62P pos and PAC1 pos CD62P pos CD63 pos ) in comparison to baseline. Coagulation markers, such as fibrinogen, D‐dimer, plasminogen activator inhibitor‐1, von Willebrand factor activity and factor VIII, were also significantly increased, an effect that was most pronounced 24 hours after the hypoglycaemic clamp. Conclusion A single event of insulin‐induced hypoglycaemia led to an increase in markers of platelet activation and coagulation in people with early stages of type 2 diabetes on metformin therapy. However, the activation occurred with a delay and was evident 24 hours and 7 days after the actual hypoglycaemic episode.